TP53 mutated myeloid malignancies and their treatment strategy

Abstract

 Mutations in the TP53 gene occur in 10-15% of AML and 10-30% of MDS and are more frequent in treatment-related neoplasms. Although TP53-mutated myeloid neoplasms usually have a very poor prognosis, TP53 mutations are also found in clonal hematopoiesis in healthy individuals, and in this case, they usually take a one-allele pattern. These mutations are assumed to develop into bi-allelic pattern after getting the second hits or accompanied by loss of heterozygosity (LOH) in the TP53 locus when they are observed in tumors. Mutations in one allele pattern can also be found in tumors, where the clinical picture, including genetic characteristics and prognosis, is like that of TP53 mutation-negative cases. TP53-mutated myeloid tumors are refractory to most treatments but respond to DNA methylation inhibitors. However, the duration of remission period is usually short, precluding prolonged survival. This has led to the development of new agents to improve remission rates and attempts to combine short remission periods with HSCT.